Dr. AAN. Subawa, Msi.

Cardiovascular disease is the leading cause

of death among adults worldwide (1996)
Coronary disease 7.2 million
Cancer 6.3
Cerebrovascular disease 4.6
Acute lower respiratory tract infections 3.9
Tuberculosis 3.0
COPD (chronic obstructive pulmonary disease) 2.9
Diarrhea (including dysentery) 2.5
Malaria 2.1
AIDS 1.5
Hepatitis B 1.2
Atherosclerosis:
a multifactorial disease
Main risk factors for coronary heart disease
Different stages of atherosclerotic plaque
development
Vascular endothelium modification
in atherosclerosis
Plaque formation
1 — Fatty streak
Plaque formation
2 — Fibrous cap
Plaque formation
3 — Lipid core
From plaque to thrombosis, key event:
plaque rupture
Vulnerable plaque
Key role of the macrophage in the degradation
of the fibrous cap
Thrombus formation
The macrophages release coagulation factors
How to reduce the risk of plaque rupture
 COMING BIOMARKERS

Apple F.S et al, Future Biomarkers Clin Chem: 5-05 14

Cardiac marker
 Cardiac troponin (the most sensitive and specific test for
myocardial damage)
 Creatine kinase (CK, also known as phosphocreatine
kinase or creatine phosphokinase)
 Aspartate transaminase (AST, also called
Glutamic Oxaloacetic Transaminase (GOT/SGOT) or
aspartate aminotransferase (ASAT))
 Lactate dehydrogenase (LDH)
 Myoglobin (Mb) has low specificify for myocardial infarction
and is used less than the other markers.
 Cardiac markers are substances released
from heart muscle when it is damaged as a
result of myocardial infarction. Depending on
the marker, it can take between 2 to 24 hours
for the level to increase in the blood.
Additionally, determining the levels of cardiac
markers in the laboratory - like many other lab
measurements - takes substantial time.
Cardiac markers are therefore not useful in
diagnosing a myocardial infarction in the acute
phase. The clinical presentation and results
from an ECG are more appropriate in the
acute situation
CARDIAC TROPONIN
 Troponin is a complex of three proteins
that is integral to muscle contraction in
skeletal and cardiac muscle, but not
smooth muscle.
 Troponin is a component of thin
filaments (along with actin and
tropomyosin), and is the protein to which
calcium binds to accomplish this
regulation.
Cardiac troponin......

 Troponin has three subunits, TnC, TnI,

and TnT:
○ Troponin C binds to calcium ions to produce a
conformational change in TnI
○ Troponin T binds to tropomyosin, interlocking
them to form a troponin-tropomyosin complex
○ Troponin I binds to actin in thin myofilaments
to hold the troponin-tropomyosin complex in
place.
Diagnostic use of Cardiac Troponin
 Certain subtypes of troponin (cardiac
troponin I and T) are very sensitive and
specific indicators of damage to the heart
muscle (myocardium).
 They are measured in the blood to
differentiate between unstable angina and
myocardial infarction (heart attack) in
patients with chest pain. A patient who had
suffered from a myocardial infarction would
have an area of damaged heart muscle
and so would have elevated cardiac
troponin levels in the blood
Cardiac troponin......

 It is important to note that cardiac

troponins are a marker of all heart
muscle damage, not just myocardial
infarction
 Technical Aspects
○ Cardiac troponin T (cTnT) and I (cTnI) are
measured by immunoassay methods.
Cardiac troponin......

 Half life biologik dan kecepatan

peningkatan cTnT dalam serum sama
seperti cTnI.
 Kadar cTnT dalam serum lebih lambat mjd
normal dibanding cTnI (kira2x 14 hari).
 cTnI  diduga hanya ditemukan pd otot
jantung
 Half life biologik cTnI: ± 2-4 jam.
 Infark miokard: cTnI meningkat 2-8 jam
setelah nyeri dada  kembali normal: 7
hari.
Creatinin kinase dan isoenzimnya
 Enzim yg ada pd pelbagai jenis jaringan
(otot).
 Konsentrasinya di otot tinggi  peran
CK untuk energi metabolisme.
 Memiliki 2 sub unit: B dan M
 Isoform:
○ CK-MB
○ CK-MM
○ CK-BB
Creatinin kinase.....

 konsentrasi CKMB tertinggi pd sel otot

jantung, berikutnya otot skletal.
 Di otot jantung: 20% CK adalah CK-MB,
sisanya CK-MM.
 Normal values are usually between 25 and
200 U/L.
Aspartate transaminase (AST)

 Nama lain:
○ serum glutamic oxaloacetic transaminase
(SGOT)
○ aspartate aminotransferase (ASAT/AAT)
 Function: it facilitates the conversion of
aspartate and alpha-ketoglutarate to
oxaloacetate and glutamate.
 Isozymes:Two isoenzymes are present in
humans. They have high similarity.
○ GOT1, the cytosolic isoenzyme derives mainly
from red blood cells and heart.
○ GOT2, the mitochondrial isoenzyme is
predominantly present in liver.
Structure of AST
 Clinical significance of AST
 It is raised in acute liver damage. It is also
present in red blood cells and
cardiac muscle.
 AST was defined as a biochemical marker
for the diagnosis of
acute myocardial infarction in 1954.
However the use of AST for such a
diagnosis is now redundant and has been
superseded by the cardiac troponins.
 AST / ALT is commonly measured clinically
as a part of a diagnostic liver function test,
to determine liver health.
 Differential Diagnosis of Causes of
Elevated AST
 Acute hepatitis Malignancy
 Alcoholic hepatopathy Myocardial Infarction
 Cholangitis Myositis
 Cholestasis Open heart surgery
 Chronic active hepatitis Perimyocarditis
 Cirrhosis Polymyositis
 Dermatomyositis Primary biliary cirrhosis
 Drugs Progressive myodystrophia
 Epstein-Barr Virus Pulmonary Embolism
 Fatty liver Renal infarction
 Hepatic tumor Seizure
 Hypothyroid myopathy Severe muscle trauma
Spasms, muscle injuries
 Malignant hyperthermi
a Strong physical work
 MYOGLOBIN
 Merupakan komponen protein terutama
untuk oksigenasi otot serat lintang.
 Jumlahnya banyak, mempunyai berat
molekul yg relatif kecil  cepat
dilepaskan ke dalam darah pd
kerusakan otot (< 1 jam).
 Petanda yg lebih sensitif daripada
troponin pd awal serangan infark
miokard akut.
 Spesifisitasnya rendah.
 Structure of myoglobin
Normal value: < 70 ng/ml
 Role in disease of myoglobin
 Myoglobin is released from damaged muscle
tissue (rhabdomyolysis), which has very high
concentrations of myoglobin.
 The released myoglobin is filtered by the
kidneys but is toxic to the renal tubular
epithelium and so may cause acute renal
failure.
 Myoglobin is a sensitive marker for muscle
injury, making it a potential marker for heart
attack in patients with chest pain. CK-MB and
TnT is used in combination with ECG, and the
clinical signs to diagnose AMI
Lactate dehydrogenase (LDH)
 It catalyses the interconversion of pyruvate and
lactate with concomitant interconversion of NADH
and NAD+.
 At high concentrations of lactate, the enzyme
exhibits feedback inhibition and the rate of
conversion of pyruvate to lactate is decreased.
Enzyme isoforms:

 LDH-1 (4H) - in the heart

 LDH-2 (3H1M) - in the reticuloendothelial system
 LDH-3 (2H2M) - in the lungs
 LDH-4 (1H3M) - in the kidneys
 LDH-5 (4M) - in the liver and striated muscle
Medical use of LDH:
 Hemolysis
 Tissue turnover
 Exudates and transudates
 Meningitis and encephalitis
 HIV and elevated LDH
LAB TEST AND MONITORING
FIRST UNTIL 24 HOURS
RAPID TEST : CARDIAC READERS FOR :
 MYOGLOBIN : 30 – 700 NG/ML  for early diagnosis.
Ready for 8 minutes
 TROPONIN : 0,1 – 2,0 NG/ML ( < 0,02 ng/ml)  for
diagnosis and prognosis
 D-DIMER : ≥ 0,5 µg/ml / CK-MB : > 24 µ/l  for
prediction and prognosis
SECOND : 3 SERIAL
 TROPONIN I OR T
 hsCRP
RELATIVE RISK CATEGORY OF hs-CRP FOR
CVD INCLUDING ACS / AMI

LOW/GOOD : < 1.0 mg/l

AVERAGE : 1.0 - 3.0 mg/l
HIGH : > 3.0 mg/l

(VALUE > 10.0 mg/l SHOWS THE EXISTANCE

OF OTHER INFECTION OR INFLAMMATION
AND SHOULD BE TREATED FOLLOWED BY
hs-CRP TESTING WITHIN 2 WEEKS)
ACS CARDIAC MARKERS
1. Chest pain or not
2. ECG : UA/NSTEMI
3. Myoglobin for early diagnosis
4. cTnI or cTnT for diagnosis and prognosis
5. hsCRP for predictor and prognosis
6. CK-MB for confirm the diagnosis :
○ cTnI and cTnT (+)
CK-MB (+) or (-) True positive
○ cTnI or cTnT (-)
CK-MB (+) False positive
 OTHERS
Parameter Diagnostic Monitoring
1. Blood Pressure >140/90 mmHg 130/85 mmHg
2. Waist Circumference ♂ > 90 cm ♂ < 90 cm
♀ > 80 cm ♀ < 80 cm
3 Life style Lack of exercise (E) E > 30 min/day
Smoking Stop Smoking
High Fat Diet Fat < 30 %
4 DM, MetS :
FPG ≥ 110 mg/dl < 100 mg/dl
HbA1C >7% ≤7%
LDL-C ≥ 130 mg/dl < 100 mg/dl
HDL-C ♂: ≤ 40 mg/dl ♂: > 40 mg/dl
♀: ≤ 50 mg/dl ♀: > 50 mg/dl

Trigliserida ≥ 150 mg/dl < 150 mg/dl

38
Brain natriuretic peptide (BNP):
petanda biokimia gagal jantung
 Disekresikan sbg prohormon pro-BNP 
dipecah menghasilkan bentuk aktif BNP.
 Kandungan asam amino:
○ Pro-BNP : 108 AA
○ BNP : 32 AA
○ ANP : 28 AA
○ CNP : 22 AA
 BNP bersifat menghambat sistem renin-
angiotensin-aldosteron, menghambat
retensi cairan.
Indikasi pemeriksaan BNP:
 Gagal jantung
 Disfungsi ventrikel pasca IMA
(prognosis)
 Kardiomiopati obstruktif hipertrofik
 Hipertrofi ventrikel kiri
 Kardiomiopati dilatasi
 Dd/ ps dengan sesak akut.
Pemeriksaan laboratorium BNP
 Dapat diukur kadar BNP atau pro-BNP
 Metode: RIA, IRMA, FIA, EIA, ICL
 Bahan: plasma darah EDTA
 Nilai rujukan NT-proBNP (dewasa):
○ ICL : 68-112 pg/ml
○ RIA dan IRMA : 0,5-30 pg/ml
 Nilai cut off : 80 pg/ml